The original aims of this grant were to investigate the effects of vasoactive peptides (angiotensin and bradykinin) on renal tubule ion and water transport. In work funded by this grant we have found the following. 1) Bradykinin, via prostaglandins, inhibits the hydroosmotic effect of vasopressin in the cortical collecting tubule at a pre-cyclic AMP level, probably at adenylate cyclase, but has no effect on Na transport. 2) Beta-adrenergic agonists via cAMP stimulate both Cl-HCO3 and Cl self-exchange in the cortical collecting tubule. 3) Cl exit across the basolateral membrane in this segment occurs conductively. 4) The red cell anion exchange protein, band 3, is present at the basolateral membrane of a subpopulation of collecting tubule cells, where it probably mediates Cl-HCO3 exchange. In the next two years we will investigate three hypothetical mechanisms by which beta-agonists and cAMP stimulate anion transport: 1) cAMP stimulates H+ secretion by stimulating the insertion of H+ pump-bearing vesicles into the cytoplasmic membrane; 2) cAMP increases a basolateral Cl conductance; 3) cAMP causes the insertion of a Cl-HCO3 exchanger into the cytoplasmic membrane. Secondly, we plan to redirect our goals slightly to the subject of chronic regulation of anion transport by in vivo acid-base disturbances. Using the combined techniques of tubule microperfusion and cytochemistry, we will address two opposing hypothetical mechanisms for reversal of cortical collecting duct HC03 transport: 1) transport elements within a given anion-transporting cell reverse their polarity; or 2) transport of anions is regulated up or down within two different types of vectorally-fixed anion-transporting cells.